We conclude that the proposed LARS-Cox procedure can be very useful in identifying genes relevant to survival phenotypes and in building a parsimonious predictive model that can be used for classifying future patients into clinically relevant high- and low-risk groups based on the gene expression profile and survival times of previous patients.

Introduction It is increasingly becoming accepted that inflammation may play an important role in the pathogenesis of Alzheimer’s disease (AD), as several immune-related genes have been associated with AD. Among these is tumor necrosis factor (TNF)-α, a proinflammatory cytokine known to play an important role in autoimmune disorders, including rheumatoid arthritis (RA). Although AD and RA appear to involve similar pathological mechanisms through the production of TNF-α, the relationship between AD and RA remains unknown. Objective To determine the relative risk of AD among RA patients and non-RA patients, and whether anti-TNF therapy for RA was associated with a lower risk of AD in RA patients. Methods We performed a nested case-control study of more than 8.5 million commercially insured adults (aged ≥18 years) in all 50 US states, Puerto Rico, and US Virgin Islands in the Verisk Health claims database. We derived a sub-cohort of subjects with a diagnosis of RA (controls), or RA and AD (cases), matching cases and controls based on age, sex, exposure assessment period, and methotrexate treatment. We also assessed relative risk of AD following exposure to standard RA therapies, including anti-TNF agents (infliximab, adalimumab, etanercept), methotrexate, prednisone, sulfasalazine, and rituximab. Odds ratios were adjusted for comorbidities, including coronary artery disease, diabetes mellitus, and peripheral vascular disease. Results AD was more prevalent (p < 0.0001) among RA patients (0.79 %) than among those without RA (0.11 %). Chronic conditions such as coronary artery disease (odds ratio [OR] 1.48; 95 % confidence interval [CI] 1.04–2.05; p = 0.03), diabetes (OR 1.86; 95 % CI 1.32–2.62; p = 0.0004), and peripheral vascular disease (OR 1.61; 95 % CI 1.06–2.43; p = 0.02) significantly increased the relative risk of AD among RA patients. Exposure to anti-TNF agents as a class, but not other immunosuppressive drugs studied, was associated with lowered risk of AD among RA patients (unadjusted OR 0.44; 95 % CI 0.22–0.87; p = 0.02; adjusted OR 0.45; 95 % CI 0.23–0.90; p = 0.02). Sub-group analysis demonstrated that of the three anti-TNF agents studied, only etanercept (unadjusted OR, 0.33; 95 % CI 0.08–0.94; p = 0.03; adjusted OR 0.30; 95 % CI 0.08–0.89; p = 0.02) was associated with a decreased risk of AD in RA patients. Conclusion There is an increased risk of AD in the studied RA population. The relative risk of AD among RA subjects was lowered in those exposed to etanercept. Anti-TNF therapy with etanercept shows promise as a potential treatment for AD.

Some serrated polyps of the colorectum are likely pre-invasive lesions, evolving through a newly recognized serrated pathway to colorectal cancer. To assess possible risk and protective factors for serrated polyps – and particularly to explore differences in risk factors between polyps in the right and left colorectum – we pooled data from three large multi-center chemoprevention trials. A serrated polyp (SP) was defined broadly as any serrated lesion (hyperplastic, sessile serrated adenoma, traditional serrated adenoma, mixed adenoma) diagnosed during each trial’s main treatment period, of about three to four years. Using generalized linear regression, we computed risk ratios and 95% confidence intervals (CI’s) as measures of the association between risk of serrated polyps and demographic, lifestyle, and dietary variables. Of the 2830 subjects that completed at least one follow-up exam after randomization, 675 (23.9 %) had at least one left sided serrated polyp and 261 (9.2 %) had at least one right sided lesion. In the left colorectum, obesity, cigarette smoking, dietary fat, total energy intake, and red meat intake were associated with an increased risk of serrated polyps. In the right colon, aspirin treatment was associated with a reduced risk and family history of polyps and folate treatment were associated with an increased risk of serrated polyps. Our results suggest that several common lifestyle and dietary variables are associated with risk of serrated polyps, and some of these may differ for the right and left colorectum.